The gut microbiome as a modulator of healthy ageing

Abstract

The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort studies across geographically distinct populations. We also address the promise of the targeted restoration of microorganisms associated with healthier ageing.

Fig. 1. Microorganism–host signalling as a contributor to healthy or unhealthy ageing.

Chronological age is accompanied by changes in host–microorganism homeostasis that determine, in part, the rate of physical and cognitive decline. Lifestyle and environmental effects on the microbiota can delay (healthy ageing) or accelerate (unhealthy ageing) deterioration in the host and foreshorten life expectancy.

Fig. 2. Physiological, social and disease-related influences on the microbiome of older people.

Progressive decline in physiological function along the alimentary tract changes the internal microenvironment in all individuals to a variable degree and indirectly affects nutrient intake by older people. Additional variables that shape the microbiome of older people include lifelong lifestyle choices, contact with the external microenvironment, social networks (the social microbiome), and the reciprocal influences of age-related diseases and their treatment.

Fig. 3. Microbiome alterations in ageing (and unhealthy ageing).

Consistent patterns of microbiome taxa alterations associated with ageing (in general) and across various aspects of healthy versus unhealthy ageing in humans. There are primarily two categories of gut microbiome versus ageing studies in humans: studies that investigate changes in the gut microbiome composition across the age landscape and studies that investigate alterations between apparently healthy and unhealthy older individuals. Based on an extensive literature survey of these two kinds of studies (Tables 2,3), three major groups of taxa showing consistent patterns of alteration (increasing or decreasing abundance in older people; increasing or decreasing abundance with unhealthy ageing) could be identified (Supplementary information). Group 1 taxa decreased with age and were associated with healthy ageing. Group 2 consisted of the pathobionts that increased with age and were associated with unhealthy ageing. Group 3 increased with age but were observed to be depleted in unhealthy ageing. It is important to note that these three groups are defined only with respect to ageing-linked microbiome alterations (from the context of this Review). CKD, chronic kidney disease; CVD, cardiovascular disease; ILI, influenza-like illness; MetS, metabolic syndrome.

Fig. 4. Functional implications of microbiome alterations on host physiology in ageing.

Metabolic capabilities of the three taxa groups are linked to unhealthy ageing-linked decline in host physiology. Graphic summary of the key metabolites or effectors produced by the three taxa groups and the effect each of these microbiome-derived entities has in either negatively or positively regulating various ageing-linked diseases and disorders. DCA, deoxycholic acid; HDAC, histone deacetylase; IsoalloLCA, isoallolithocholic acid; LCA, lithocholic acid; LPS, lipopolysaccharide; p-Cresol, para-cresol; ROS, reactive oxygen species; TMA, trimethylamine; TMAO, TMAO, trimethylamine-N-oxide.

Fig. 5. Microbiome-associated interventions to prevent unhealthy ageing.

Pictorial summary showing examples of how specific intervention strategies have been shown to alter the microbiome alterations that prevent the ageing-associated decline in host physiology. AXOS, arabinoxylan-oligosaccharide; DCA, deoxycholic acid; GOS, galactooligosaccharide; LCA, lithocholic acid; MCT1, monocarboxylate transporter 1; p-Cresol, para-cresol; TMA, trimethylamine; XOS, xylooligosaccharides.

Fig. 6. Strategies for the formulation of personalized microbiome reconstruction strategies in older people.

a | Conceptual framework for applying personalized microbiome reconstruction strategies tailored to the extent of microbiome decline in a person with unhealthy ageing, and the factors that mediate the response of the host to these intervention strategies. b | Graphical summary of the protocol to identify interactions between host phenotype, baseline microbiome and the overall response to an intervention and to enable the design of predictive strategies for host response and personalized intervention therapies.